This invention relates generally to antiviral agents and more particularly to a new antiviral agent comprising 1-.beta.-D-arabinofuranosylthymine as a therapeutically efficacious component and prepared in a pharmaceutical form for absorption through the alimentary canal of the human or lower animal to be treated.
Representative examples of antiviral agents heretofore known are 5-iodo-2'-deoxyuridine (hereinafter referred to by the abbreviation "IDU") and 9-.beta.-D-arabinofuranosyladenine (hereinafter abbreviated "ara-A"). IDU, however, produces side effects such as teratosis and by no means can be said to be a safe antiviral agent. Similarly as in the case of IDU, ara-A also strongly inhibits growth of animal cells including those of humans and is also reported to give rise to teratosis, whereby its toxicity is a cause of concern when it is employed as a medicinal remedy.
On one hand, 1-.beta.-D-arabinofuranosylthymine (hereinafter abbreviated "ara-T") is known to exhibit high antiviral activity in vitro against herpes simplex virus (HSV) and varicella-zoster virus (VZV) as reported in Virology, Vol. 65, p. 294 through p. 296 (1975); Antimicrobial Agents and Chemotherapy, Vol. 12, p. 243 through p. 254 (1977); and Journal of Virology, Vol. 23, p. 679 through p. 684 (1977). As for the antiviral activity in vivo of ara-T, the only report I am aware of is that concerning a therapeutic experiment with hamsters infected with equine abortion virus (EAV). See Antimicrobial Agents and Chemotherapy, Vol. 12, p. 243 through p. 254 (1977); and Annals, New York Academy of Science, Vol. 284, p. 342 through p. 350 (1977).
Anti-DNA virus agents used for clinical treatments or undergoing clinical experiments at present are being administered by non-oral methods such as intravenous administration, and there appear to be none that are effective when administered orally. It is considered that, in general, an inhibitor of DNA synthesis exhibits its efficacy more when administered by a non-oral method than when it is administered orally. Therefore, an antiviral activity test in vivo of ara-T is also being carried out by non-oral administration such as intraperitoneal administration, and there have been no reports whatsoever of its oral administration.
As a result of various studies I have carried out with the aim of developing antiviral agents of high efficacy yet low toxicity, I discovered that, when ara-T was administered orally, it exhibited a much more effective antiviral activity and less toxicity than when administered by a non-oral method, and, therefore, a ratio of its tolerance dosage to the effective concentration for treatment became much greater. Furthermore, it was also verified that, when ara-T was orally administered to mice, it was absorbed through the digestive system and was retained at a considerably high concentration in the blood for a definite time.
Accordingly, it was confirmed that the method of orally administering ara-T thereby to cause it to be absorbed into the body through the alimentary canal is an extremely effective method of treating DNA viral infections.